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Keywords:

  • coffee;
  • fibrotic severity;
  • hepatocellular carcinoma;
  • liver inflammation;
  • non-alcoholic fatty liver disease

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References

Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References

Coffee is a brewed beverage with a distinct aroma and flavor, prepared from the roasted seeds of the coffee plant. It has been part of the human diet since the 15th century. In its various forms (including decaffeinated coffee), coffee is one of the most consumed drinks in the world, partly for its mild mood-enhancing and stimulatory effects on the central nervous system. Caffeine, one of the main constituents of coffee, has been shown to have a wide spectrum of biological activities. The effects of coffee on chronic liver disease, especially in lowering the risk of developing hepatocellular carcinoma (HCC) has recently attracted considerable attention.

During the last 20 years, several investigators have focused on the potential beneficial health effects of coffee, especially against liver disease. In 1992, Klatsky and Armstrong reported an inverse relationship between coffee drinking and the risk of cirrhosis in a 10-year follow-up study of a large number of subjects using multivariate analysis by Cox proportional hazards model.[1] Coffee drinking also decreased the risk of clinically significant chronic liver disease.[2] Other studies show that coffee drinkers (at least 3 cups/day) had significantly lower levels of gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), serum alkaline phosphatase, and bilirubin concentration compared with non-coffee-drinking subjects or those consuming less than three cups daily.[3] Coffee consumption has also been associated with decreased blood GGT levels in humans, and reported to confer possible hepatoprotection against alcoholic liver disease.[4, 5]

On the other hand, authors found caffeine intake did not appear to affect liver stiffness (detected by transient elastography) in patients with chronic hepatitis B virus (HBV).[6] A preliminary conclusion from these observations is that if coffee has a protective effect against cirrhosis in HBV infection, this is not as significant as the viral determinants of chronic liver disease.

More than 180 million people worldwide are chronically infected with the hepatitis C virus (HCV), and approximately 350 000 people die every year from HCV-related liver disease, such as decompensated cirrhosis and/or HCC. Some case–control studies have shown that coffee consumption is associated with reduced risk of HCC among HCV-infected patients.[7, 8] Costentin et al. found that caffeine consumption of > 408 mg/day (≥ 3 cups coffee) was associated with reduced histological activity in patients with chronic HCV infection.[9] However, there was no relationship between coffee consumption and fibrosis severity.[9] Finally, coffee consumption may improve virological response to pegylated-interferon and ribavirin antiviral treatment.[10, 11]

Coffee consumption may be associated with a reduced risk of HCC.[12-16] This relationship appears to be very consistent, and the effect is a powerful one. Thus, four meta-analyses found that inverse relationship between coffee and HCC risk.[17-20] Further, the relationship between coffee intake and decreased risk of HCC has been observed for several etiological types of chronic liver disease. In those with chronic HBV infection, moderate coffee consumption (drinking coffee ≥ 4 times/week) was associated with a reduced risk of HCC by half (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.30–0.97) with a significant dose–response effect (χ2 = 5.41, df = 1, P = 0.02).[21] In another hospital-based case–control study, it was found that a high lifetime coffee consumption (≥ 20 000 cups) was an independent protective factor against HCC in all subjects. However, high levels of coffee consumption did not significantly affect HCC risk in patients with HBV (OR = 0.64, 95% CI: 0.36–1.14) after adjustment for HBeAg status, serum HBV DNA level, and antiviral therapy.[22]

The prevalence of non-alcoholic fatty liver disease (NAFLD) is escalating rapidly worldwide in association with such metabolic disorders as type 2 diabetes mellitus (T2DM), obesity, hypertension, and hyperlipidemia (metabolic syndrome). NAFLD comprises a pathological spectrum characterized by fat accumulation within the liver known as simple steatosis, or “non-NASH NAFLD,” and/or in combination with varying degrees of hepatocellular injury manifested by ballooning, inflammation, liver fibrosis, cirrhosis, and HCC. In NAFLD-related cirrhosis, liver histology may no longer show inflammation or even steatosis, and this likely represents the largest proportion of cases often referred to as “cryptogenic cirrhosis.” The diagnosis of NAFLD is usually made by abnormal liver tests and hepatic imaging showing features of fatty infiltration (“bright liver”) in the context of obesity, a family history of diabetes, and/or features of metabolic syndrome; as well, other causes of liver disease and significant alcohol intake must be excluded.

Several studies of hepatic lipid metabolism, insulin resistance, mitochondrial dysfunction, oxidative stress, as well as genetic predisposition to altered cell metabolism and injury have contributed to current understanding of NAFLD.[23] Lifestyle measures directed at increasing physical activity (which counters insulin resistance) and weight loss remain the cornerstone of management. Notably, the effects of pharmacotherapy are still contentious; most agents studied are either modest in their effects, such as vitamin E, pioglitazone, ezetimibe, or pentoxifyllne, or have no beneficial long-term hepatoprotective effects (e.g. metformin, ursodeoxycholic acid). In general, moderate energy and simple carbohydrate restriction, reduction of total and saturated fat intake, along with increasing physical activity are beneficial and highly recommended. Interestingly, recent studies have shown that coffee drinking may be protective against NAFLD-related chronic liver disease and possibly, HCC.

Sources of information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References

This systematic review is the first that we are aware of to focus on the epidemiology, magnitude, and mechanisms of possible beneficial effects of coffee consumption in patients with NAFLD. Using “liver disease” and “coffee” as search terms in the PubMed database, 240 articles were returned. The abstracts of all these articles were reviewed, and 12 studies that evaluated relationship between NAFLD and coffee were examined in detail. Specific questions pertaining to this area of research were evaluated, as indicated below. The number of articles published about coffee and liver disease has increased steadily since 2003 (Fig. 1).

figure

Figure 1. Number of publications related to coffee intake and liver disease in the past decade.

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Relationship between coffee consumption and NAFLD in community studies

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References

Four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES, USA 2001–2008) were used to investigate the effects of dietary behavior in NAFLD patients. Dietary intake was evaluated by questionnaires that included nutrition components. Multivariate analyses were conducted of variables that included demographics, clinical parameters, and nutritional components in relation to presence of NAFLD (defined in this study by elevated aminotransferase, without ultrasonography). Five factors were independently associated with NAFLD: African American race, male gender, obesity, caffeine intake, as well as plain water consumption. These findings show a strong association between coffee consumption and protection against the development of NAFLD[24] (see Table 1). The limitation of the NHANES data analysis is the restricted define of NAFLD; cases with cirrhosis may not have shown elevated ALT.

Table 1. Relationship between coffee consumption and non-alcoholic fatty liver disease (NAFLD) in community studies
Authors (Reference)SubjectsDesignResultsComments
  1. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BLS, bright liver score; MVA, multivariate analysis; NASH, non-alcoholic steatohepatitis; NHANES, National Health and Nutrition Examination Surveys.

Birerdinc A et al.[24] 2012; USA1 782 NAFLD; 16 768 controls from 4 continuous cycles of NHANESNAFLD defined by ALT/AST exclusive of other liver diseaseCaffeine intake in NAFLD 165 ± 6.55 mg, controls 188 ± 4.90 mg (P = 0.0006). MVA showed caffeine intake an independent predictor of NAFLD (OR = 0.999, 95% CI: 0.999–1.00, P = 0.0003)Minor effect in lowering prevalence of NAFLD
Catalano D et al.[25] 2010; Italy137 NAFLD; 108 controls.Assessed by ultrasound BLS, with exclusion criteria

BLS less in coffee drinkers than in non-coffee drinkers. Coffee consumption as cups/day (0/< 3/≥ 3) per groups by BLS:

severe: 9/7/0; moderate: 12/37/33;

light: 9/21/29 (P < 0.0001)

Inverse association between coffee intake and degree of BLS
Gutierrez-Grobe, Y et al.[26] 2012; Mexico

57 NAFLD

73 controls.

Case control study

Assessed by ultrasonography

Dietary history questionnaire.

Coffee intake(log caffeine) between different severity of NAFLD:

severe steatosis: 0.15 ± 0.05;

moderate steatosis: 1.58 ± 0.72;

mild steatosis: 1.61 ± 0.79;

no steatosis: 1.75 ± 0.70(P ≤ 0.05)

High coffee intake associated with lower grade NAFLD
Molloy JW et al.[27] 2012; USA

36 NASH stage 2–4;

61 NASH stage 0–1;

83 bland steatosis;

126 controls

Biopsied NAFLD cases. Validated caffeine questionnaire

Coffee caffeine intake (mg/day):

NASH stage 2–4: 153;

NASH stage 0–1: 256;

bland steatosis: 160;

controls: 228. (r = −0.215, P = 0.035).

Negative correlation between caffeine intake and stage of fibrosis

In an Italian study, 137 NAFLD cases and 108 controls were enrolled, and coffee intake determined by the absolute number of cups of coffee consumed. This was graded as 1 (0 cups of coffee/day), 2 (1–2 cups of coffee/day), and 3 (≥ 3 cups of coffee/day). Insulin resistance was analyzed by homoeostasis model assessment-insulin resistance (HOMA-IR) index. When compared with non-coffee drinkers, those who consumed coffee had less severe fatty liver evaluated by ultrasound “bright liver score” (BLS). Further, obesity, insulin resistance, lower high-density lipoprotein (HDL) cholesterol, older age, and arterial hypertension were associated with a greater risk of more severe grades of BLS, while coffee intake was associated with a lower risk of severe BLS. By multiple regression analysis, coffee use was inversely associated with the degree of “bright liver,” while insulin resistance and obesity were directly associated with increased likelihood and severity of BLS on ultrasound.[25] A case–control study from Mexico also found similar protective effects of coffee consumption against NAFLD as assessed by ultrasonography[26] (Table 1). The limitations of these studies are the insensitivity of ultrasound for minor grade of steatosis and possibly for established cirrhosis when steatosis may be resolved.

The association of caffeine consumption with both the prevalence and severity of NAFLD was further established in another study where a validated questionnaire of caffeine consumption was utilized to determine if there was a relationship between caffeine intake and NAFLD severity, this time established by histological examination of liver biopsies. In this study, the authors reported a strong inverse relationship between caffeine consumption and hepatic fibrosis[27] (Table 1).

Mechanisms by which coffee may reduce severity of NAFLD

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References

Despite the persuasive epidemiological data, particularly for ultrasound and histological studies, the cellular and molecular mechanisms underlying the effects of coffee consumption in patients with NAFLD remain undefined. Antioxidant, anti-inflammatory, antifibrotic, and altered energy metabolism have been potentially implicated.

Prior to examining these possible effects of coffee on NAFLD, a consideration of coffee constituents is important. The basic chemical composition of coffee depends on its species and physiological aspects. The main bioactive compounds and their effects on liver disease are listed in Table 2 and have been reviewed.[24, 27-35]

Table 2. List of chemical composition of coffee proposed biological effects
ConstituentsEffectsReferences
  1. CPP, coffee polyphenol; PPAR-α, peroxisome proliferator activated receptor α; SREBP-1c, sterol regulatory element-binding protein-1c.

Carbohydrates and fiber

 Sucrose

 Reducing sugars

Most non-digestible, the digestible carbohydrate fraction is negligible.[28]

Nitrogenous compounds

 Protein/peptides

 Free amino acids

 Caffeine

 Trigonelline

Caffeine: stimulation of hepatic lipid metabolism, induction of thermogenesis, anti-oxidative stress, anti-fibrosis[24, 27, 28]

Lipids

Coffee oil

Diterpenes (Cafestol and Kahweol)

Cafestol and Kahweol: cholesterol raising, anti-carcinogenesis[29, 30]
MineralsPotassium: reducing hypertension but in minimal amount[28]

Acids and esters/polyphenol

 Chlorogenic acids

 Aliphatic acids

 Quinic acid

CPP: enhancing energy metabolism, reducing lipogenesis, downregulating SREBP-1c

Chlorogenic acids: the predominant antioxidant in coffee; reducing hepatic glucose output, lowering cholesterol, attenuating fatty liver and upregulating PPAR-α

[28, 31-33]
MelanoidinsAnti-oxidation, anti-inflammation, and increase expression of adiponectin receptor and PPAR-α[34, 35]

Coffee and T2DM

Individuals with T2DM have higher incidence of NAFLD, while NAFLD exacerbates hepatic insulin resistance and increases the risk of developing T2DM.[36, 37] To date, systematic reviews and meta-analysis have indicated that higher coffee consumption is consistently associated with a lower risk of T2DM. This association does not depend on race, gender, geographic distribution of the study populations, or the type of coffee consumed.[38-41] The mechanism(s) for this strong protective effect of coffee on T2DM is still needed to be elucidated. High coffee consumption was associated with greater insulin sensitivity in several but not all cross-sectional studies.[40] Increased plasma adiponectin, antioxidation, anti-inflammation, and thermogenic effect of coffee may contribute to the lower risk of T2DM.[41, 42]

Coffee and oxidative injury

Of interest, there have been several studies which indicate that coffee consumption is inversely related to the incidence of diseases in which reactive oxygen species (ROS) are involved. It is postulated that the antioxidant properties of coffee may account for this phenomenon. Vitaglione et al.[34] established a high-fat-diet (HFD)-induced non-alcoholic steatohepatitis (NASH) model in male Wistar rats to study the protective mechanisms of coffee, or its component polyphenols or melanoidins against NAFLD. Biomarkers of antioxidant status measured in both serum and liver samples show that HFD-fed rats had significantly higher concentrations of oxidized glutathione (GSSG) than control rats. Coffee, polyphenols, or melanoidins reduced GSSG concentrations in HFD-fed rats supplemented with coffee in their drinking water compared with those given water only. Likewise, serum malondialdehyde concentration was significantly higher in rats in the HFD group than in control rats (2.03 ± 0.14 μM vs 1.47 ± 0.12 μM). Coffee consumption (1.50 ± 0.09 μM) or polyphenols (1.62 ± 0.08 μM) returned these levels to control values. Further, there was a significant increase in antioxidant capacity in rats treated with polyphenols in drinking water compared with controls (0.36 ± 0.02 mM Trolox® equivalent [TE] vs 0.32 ± 0.01 mM TE).[34]

Goya L et al. investigated the potential protective effect of coffee melanoidins, in particular, a water-soluble high-molecular weight fraction, on the redox status of cultured human HCC, HepG2 cells. The results show that coffee melanoidins conferred significant protection against oxidative insults.[35]

To establish whether coffee consumption protects humans against oxidative DNA damage, a cross-over intervention study was conducted. In this trial, 38 participants consumed 800 mL coffee (or water in controls) daily over 5 days. DNA damage was measured in peripheral lymphocytes. The extent of DNA migration attributable to formation of oxidized purines (also known as formamidopyrimidine glycosylase sensitive sites) was decreased by 12% after coffee intake (P = 0.006). These findings suggest that coffee consumption prevents endogenous formation of oxidative DNA damage in humans. While this observation may be causally related to the beneficial health effects of coffee, biochemical indices of redox status such as malondialdehyde, 3-nitrotyrosine and total antioxidant levels in plasma, glutathione concentrations in blood, intracellular ROS levels, and the activities of superoxide dismutase and glutathione peroxidase in lymphocytes were not markedly altered at the end of the trial.[43]

Investigators have observed different levels of oxidative DNA damage and DNA repair in the livers of coffee-fed mice.[44] In one study, lean male mice were fed 0.1% (w/v) instant coffee solution prepared weekly with 60°C tap water. At 2, 4, and 8 months, there was no difference in the hepatic levels of 8-hydroxydeoxyguanosine (8-OH-dG, a marker of oxidative DNA damage) and 8-OH-dG repair-associated genes, redox system-associated genes, and hepatic lipoperoxide levels between the coffee-fed and control groups of mice. These results suggest that instant coffee consumption has little, if any, effect on hepatic oxidative stress in lean mice. Similarly, others report little or no significant difference in catalase (0.2 ± 0.7 vs 0.3 ± 0.7 nM/min/mL) levels, superoxide dismutase (4.7 ± 2.1 vs 5.4 ± 3.4 U/mL), or thiobarbituric acid-reactive substances (3.9 ± 1.5 vs 4.0 ± 1.8 μM/mL) between NAFLD and controls. Hence, while coffee intake has a protective effect against severity of NAFLD, the weight of evidence (albeit, currently incomplete) is that coffee's positive effects are unlikely to be attributable to any differences in antioxidant variables.[26]

Coffee and liver inflammation

Coffee intake has been associated with reduced levels of abnormalities in serum aspartate aminotransferase (AST), ALT,[45-47] and GGT.[48] Fukushima Y et al.[49] conducted a study where mice were fed HFD to induce NAFLD, then treated with or without coffee (1.1% decaffeinated/caffeine-containing instant coffee). Mesenteric fat weight was lower in the HFD+coffee group than those fed a HFD without coffee (P < 0.05). Further, serum AST and ALT levels were significantly lower in the HFD+coffee group than in mice fed a HFD only (P < 0.05). Pro-inflammatory interleukin-1beta (IL-1β) gene expression in murine liver was upregulated in the HFD group and was significantly downregulated by coffee consumption (P < 0.01). Expression of monocyte chemoattractant protein-1 in liver and adipose was also suppressed in the HFD+coffee group. Hence, coffee consumption appears to significantly reduce hepatic pro-inflammatory response.

In a separate study, co-administration of coffee with a HFD in rodents appeared to reduce tumor necrosis factor-α (TNF-α), tissue transglutaminase, and transforming growth factor β (TGF-β) expression in the liver, and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α. Coffee also lowered hepatic concentrations of TNF-α, interferon-γ and increased anti-inflammatory cytokines, IL-4, and IL-10.[34]

Coffee and hepatic fibrosis

Few studies have discussed the influence of coffee on liver fibrosis in NAFLD. In a recent European study, 195 morbidly obese patients referred for bariatric surgery were assessed.[50] Liver biopsies showed NASH in 19%, and significant fibrosis in 35%. By logistic regression analysis, regular coffee intake was an independent factor negatively associated with significant fibrosis in a model that included AST, HOMA-IR, presence of the metabolic syndrome, and NASH. Interestingly, the consumption of regular coffee (but not espresso) was associated with an earlier stage of fibrosis and was independently protective against fibrosis.[50] Sucrose, which is composed of glucose and fructose, is often added by espresso consumers to their coffee and the authors noted that this may have potentially countered coffee's positive effects in this study, particularly by the potential detrimental effect of fructose on NAFLD. Thus, fructose consumption has been noted to aggravate the severity of liver fibrosis in North American patients who have NASH.[51, 52]

Few studies have addressed the mechanism for the possible anti-fibrotic effects of coffee on liver fibrosis in NAFLD. In NASH-associated fibrosis, the principal cell type responsible for extracellular matrix production is the hepatic stellate cell.[53] The mechanisms of fibrogenesis in the liver are dependent on an interplay of many pro-fibrotic and anti-fibrotic cytokines and growth factors. TGF-β is one such pro-fibrogenic growth factor. In turn, TGF-β can activate connective tissue growth factor (CTGF) which is also responsive to insulin and other metabolic factors in NAFLD, and which can also mediate matrix production.[54] Caffeine inhibits CTGF synthesis in hepatocytes and liver non-parenchymal cells, primarily by inducing degradation of Smad2, thereby interrupting TGF-β signaling.[55]

Coffee and hepatic metabolism

The liver plays diverse and crucial roles in lipogenesis, gluconeogenesis, and cholesterol metabolism.[37] In a rodent model that develops metabolic syndrome and NAFLD when fed a high-carbohydrate, HFD, supplementation with Colombian coffee extract improved glucose tolerance, decreased hypertension, induced cardiovascular remodeling, and attenuated NAFLD severity. Of note, these changes were not associated with weight loss or reduction of serum lipids in the animals.[56] Interestingly, one study reported that some coffee brewing techniques raise serum total and low-density-lipoprotein cholesterol concentrations in humans.[29] The diterpene lipids, cafestol, and kahweol (also main constituents of coffee) were considered to be the responsible lipid-altering factors. In contrast, filtered coffee does not appear to affect serum cholesterol, and this is thought to be related to the removal of diterpenes by the filtration process (filter paper).[29]

Adiponectin is an adipokine that governs insulin sensitivity and has potent anti-inflammatory effects. Plasma adiponectin levels are often lower in patients with NAFLD, and correlate inversely with the severity of steatosis and NASH. In a cross-sectional study comprised of 2554 male and 763 female Japanese workers, associations between coffee consumption and adiponectin, leptin, markers for subclinical inflammation, glucose metabolism, lipids, and liver enzymes were ascertained. The findings revealed that coffee consumption was associated with higher serum adiponectin and lower serum leptin levels.[57]

Coffee is also enriched with polyphenols (coffee polyphenols, CPP). The effects of CPP on diet-induced body fat accumulation was investigated, and C57BL/6J mice were fed either a control diet, HFD, or HFD supplemented with 0.5–1.0% CPP for 2–15 weeks. Supplementation of a HFD with CPP significantly reduced body weight gain, abdominal and liver fat accumulation, as well macrophage infiltration into adipose. Energy expenditure, evaluated by indirect calorimetry, was significantly increased in CPP-fed mice. The hepatic transcript levels of sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1, and pyruvate dehydrogenase kinase-4 were also significantly reduced in CPP-fed mice compared with HFD mice. CPP has also been shown to suppress the expression of SREBP-1c in Hepa 1–6 cells, with a concomitant increase in microRNA (miR)-122. Structure–activity relationship studies of nine quinic acid derivatives isolated from CPP in Hepa 1–6 cells also suggest that mono- or di-caffeoylquinic acids may have potent and potentially beneficial effects.[33] Thus, it appears that CPP enhances energy metabolism, reduces lipogenesis by downregulating SREBP-1c and related signaling pathways, thereby suppressing the accumulation of body fat and newly synthesized (saturated) fatty acids in the liver.[33]

Conclusions and future perspectives

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References

Taken together, these studies provide reasonably strong evidence for a protective effect of coffee consumption on development of NAFLD, and on reducing its severity in NASH. Since the most convincing effect of coffee consumption on other forms of liver disease is its association with a substantially reduced rate of HCC, future studies on HCC in NAFLD examining coffee consumption with other potential environmental factors (fructose, vegetables, smoking, vitamin D, and selenium, etc.) are keenly awaited. Meanwhile, it does appear that possible hepatoprotective effects of coffee are related more to polyphenols not caffeine. The possible protective effects of coffee bean polyphenols may be related to a diverse range of mechanisms, including anti-oxidant, anti-inflammatory, anti-fibrotic pathways as well as modulation in energy metabolism, reduced insulin resistance, and reduced severity of diabetes (Fig. 2). However, studies to date have been exploratory and confined to a limited range of experimental systems, only a small subset of which have utilized clinically relevant experimental models of NASH. It is clear that some components of coffee other than caffeine may be involved, and specific identification of these compounds require more rigorous study to elucidate the mechanisms underlying coffee's hepatoprotective effects in patients with NAFLD.

figure

Figure 2. Schematic diagram illustrating the mechanisms underlying coffee's potential hepatoprotective effects in non-alcoholic fatty liver disease. CTGF, connective tissue growth factor; GSSG, oxidized glutathione; IFN-γ, interferon-γ; IL-10, interleukin-10; IL-1β, interleukin-1β; IL-4, interleukin-4; MCP-1, monocyte chemoattractant protein-1; NASH, non-alcoholic steatohepatitis; PPAR-α, peroxisome proliferator-activated receptor α; ROS, reactive oxygen species; Smad2, Mothers against decapentaplegic homolog 2, SMAD family member 2; SREBP-1C, sterol regulatory element-binding protein-1C; TGF-β, transforming growth factor β; TNF-α, tumor necrosis factor α.

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References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Sources of information
  5. Relationship between coffee consumption and NAFLD in community studies
  6. Mechanisms by which coffee may reduce severity of NAFLD
  7. Conclusions and future perspectives
  8. References